The Origin of a New Progenitor Stem Cell Group in Human Development.

The observation of two precursor groups of the early stem cells (Groups I and II) leads to the realization that a first amount of fetal stem cells (Group I) migrate from the AMG (Aortal-Mesonephric-Gonadal)-region into the aorta and its branching vessels. A second group (Group II) gains quite a new significance during human development. This group presents a specific developmental step which is found only in the human. This continuation of the early development along a different way indicates a general alteration of the stem cell biology. This changed process in the stem cell scene dominates the further development of the human stem cells. It remains unclear where this phylogenetic step first appears. By far not all advanced mammals show this second group of stem cells and their axonal migration. Essentially only primates seem to be involved in this special development.

C and APUD cells and endocrine tumours. Pearse's laboratory in the years 1965-1969: a personal recollection.

This paper is a personal recollection of the studies, conducted in Prof. Pearse's laboratory in London in the years 1965-1969, which led to the discovery of production of calcitonin by parafollicular C cells and medullary carcinomas of the thyroid. The author's intention is to underline the combination of technical excellence, brilliant intuition, dedication and serendipity which led to a series of major discoveries and, historically, established the pivotal role to be played by immunohistochemistry in endocrine research and diagnosis. The formulation of Pearse's APUD cell theory gave a formal credence to the existence of common endocrine mechanisms, molecular markers and structural features in dispersed cells, all belonging to a diffuse endocrine system. This represented a major breakthrough which primed, in the following years, the studies on polypeptide hormone-producing cells and tumours, thus paving the way to the endocrine histology and pathology as we know, and practice them today.

[Disperse endocrine system and APUD concept].

This review describes the problems of disperse endocrine system and APUD-system morphology, summarizes some debatable issues of single endocrine cell biology. The data presented refer to the history of both systems discovery, morphological methods of their study, developmental sources, their structural organization and physiological roles of their cells. The significance of single endocrine cells in the regulation of the organism functions is discussed.

[Role of neuroendocrine cells in prostate cancer progression]. / Ruolo delle cellule neuroendocrine nella progressionedel carcinoma prostatico.

Neuroendocrine (NE) cells represent the third epithelial cell type on normal prostatic tissue (in addition to basal and secretory cells). They are localized in all regions of the human prostate at birth but rapidly decrease in the peripheral prostate after birth, and then reappear at puberty. After puberty, their number seems to increase until an apparently optimum level is reached, which persists between the age of 25 and 54. NE cells were defined by Pearse as APUD to refer to chemical characteristics of amine precursor uptake and decarboxylation, common to the cells of this system. The most predominant product of prostatic NE cells is Chromogranin A, but they also produce serotonin, CgB, secretogranin or CgC, thyroid-stimulating hormone-like peptide, calcitonin, katacalcin, PTHrP and a-human chorionic gonadotropin-like peptide. NE cells in normal and neoplastic prostates are devoid of androgen receptors, but they express epidermal growth factor (EGF) receptor and c-erbB-2. For these reason NE cells are androgen-insensitive. The NE component of prostate adenocarcinoma is resistant to hormone therapy; some studies showed that the number of NE tumor cells and CgA serum levels increase with the recovery of human prostate tumor from hormonal therapy. Currently there are no clinical data available to support an active role of radiotherapy in NE differentiation.

Distribution and morphology of argyrophilic cells in the digestive tract of the African ostrich.

We used light microscopy to elucidate the morphological features of argyrophilic cells in the digestive tract of the African ostrich (Struthio camelus). The results indicated that argyrophilic cells were found to be distributed among the epithelial cells of the mucosa or glands throughout the digestive tract, except for the esophagus; two types of argyrophilic cells were found; i.e., closed-type cells and cells with triangular or elongated shapes and with their apical cytoplasmic process in contact with the lumen (open-type cells); the greatest number of argyrophilic cells was found in the proventriculus, and the argyrophilic cell density gradually decreased from the proventriculus to the rectum; Furthermore, the number of argyrophilic cells in the duodenum and ileum was higher than that in the jejunum. This text still combined the characteristics that the argyrophilic cells in digestive tract of ostrich maybe related to different digestive function of different region and the basis of their morphology to carry on a discussion. It was speculated that argyrophilic cells in the digestive tract may have both endocrine and exocrine functions.

[Positron emission tomography in neuroendocrine tumours]. / Positronemisjonstomografi ved nevroendokrine svulster.

BACKGROUND: Neuroendocrine tumours constitute a small group of malignancies; about 200 new patients are diagnosed in Norway annually. This article discusses problems associated with use of deoxyfluoroglucose (FDG) Positron Emission Tomography (PET) and other available options in patients with these conditions, as well as challenges related to introduction of new radiopharmaceutical agents. MATERIAL AND METHODS: The article is based on review of literature in connection with development of new guidelines for nuclear medicine examinations, supplemented with literature identified through a non-systematic search of Pubmed. RESULTS: A large proportion of these tumours grow slowly, and recent data show that 5-year survival is about 50 %. Neuroendocrine tumours are characterised by specific biochemical processes that enable tailoring of radiopharmaceutical agents for PET and consequently a more accurate diagnosis and improved follow-up of these patients. INTERPRETATION: As for other cancer types, diagnostics and detection of metastases are an important factor for correct treatment of neuroendocrine tumours. PET with FDG is of limited use for patients with this condition. New specific radiopharmaceutical agents for PET may imply detection of 90 % of all such tumours.

[The role of diffuse endocrine system and colonocytes cellular renovation in formation of clinical variants of irritable colon syndrome in young persons].

60 patients with irritable colon syndrome (ICS) were examined. They were divided into 2 groups. Group 1 included 30 patients who had ICS with dominating constipation (ICSc). Group 2 consisted of 30 patients with ICS and dominating diarrhea (ICSd). 12 practically healthy persons composed control group. The patients were being observed in dynamics (in periods of aggravation and remission), under uniform program including clinical, endoscopic, morphologic and immunohistochemical methods. It was established that ICSc development related to hyperplasia and hyperfunction serotonin producing cells together with decrease of number and functional activity of VIP-producing cells and mast cells. It was detected significant increase of colonocytes proliferative activity, shown throw number of immunopositive to cycline Dl epithelial cells, and compensatory increase of apoptosis activity. In patients with ICSd it was registered increase of number and functional activity of general population of apudocytes, serotonin-, melatonin- and VIP-produsing cells and mast cells. It was detected decrease of number of colonocytes immunopositive to cycline D1 and proliferating cell nuclear antigen, and growth of colon epithelial cells apoptosis activity. More significant changes of diffuse endocrine system in patients with ICSd set conditions for progress of changes of cell renovation with frequent colon mucous tunic atrophy, acting as a background for carcinogenesis.

Evolution of the diffuse neuroendocrine system--clear cells and cloudy origins.

As early as the 2nd century, Galen proposed that 'vital spirits' in the blood regulated human bodily functions. However, the concept of hormonal activity required a further 18 centuries to develop and relied upon the identification of 'ductless glands', Schwann's cell and the recognition by Bayliss and Starling of chemical messengers. Bernard's introduction of 'internal secretion' and its role in homeostasis laid a physiological basis for the development of endocrinology. Kocher and Addison recognized the consequences of ablation of glands by disease or surgery and identified their necessary role in life. Detailed descriptions of the endocrine cells of the gut and pancreas and their putative function were provided by Heidenhain, Langerhans, Laguesse and Sharpey-Schafer. Despite the dominant 19th century concept of nervism (Pavlov), in 1902, Starling and Bayliss using Hardy's term 'hormonos' described secretin and in so doing, established the gut as an endocrine organ. Thus, nervism was supplanted by hormonal regulation of function and thereafter numerous bioactive gut peptides and amines were identified. At virtually the same time (1892), Ramón y Cajal of Madrid reported the existence of a group of specialized intestinal cells that he referred to as 'interstitial cells'. Cajal postulated that they might function as an interface between the neural system and the smooth muscles of the gut. Some 22 years later, Keith suggested that their function might be analogous to the electroconductive system of the heart and proposed their role as components of an intestinal pacemaker system. This prescient hypothesis was subsequently confirmed in 1982 by Thuneberg and a decade later Maede identified c-Kit as a critical molecular regulator in the development and function of the interstitial cells of Cajal and further confirmed the commonality of neural and endocrine cells. The additional characterization of the endocrine regulatory system of the GI tract was implemented when Feyrter (1938) using Masson's staining techniques, identified 'helle Zellen' within the pancreatic ductal system and the intestinal epithelium and proposed the concept of a diffuse neuroendocrine system. Pearse subsequently grouped the various cells belonging to that system under the rubric of a unifying APUD series. Currently, the gut neuroendocrine system is viewed as a syncytium of neural and endocrine cells sharing a common cell lineage whose phenotypic regulation is as yet unclear. Their key role in the regulation of gastrointestinal function is, however, indubitable.

[Morphofunctional regeneration of epithelial cells in the colon and apudocytes in the pathogenesis and prognosis of the course of non-specific ulcerous colitis].

One hundred twenty patients with nonspecific ulcerative colitis (NUC) were examined. The patients were divided into three groups equal in number according to the severity of the disease. The controls were 24 practically healthy individuals, 64 patients with irritated bowel syndrome (IBS) without pathological changes in the colon mucosa, and 64 IBS patients with atrophic or inflammatory changes in the colon mucosa. The study showed that the development of NUC was associated with an abrupt decrease in the level of proliferation markers (cycline D, and proliferating cell nuclear antigen - PCNA) in the epithelial cells of the sigmoid colon. Their number progressively decreases in more severe cases, while cell apoptosis intensifies. Such changes in cell renewal are closely connected with the functional and structural rebuilding of the diffuse endocrine system, which manifests in an increase of the total number of apudocytes as well as serotonin- and melatonin-producing cells together with a decrease in the number of VIP-producing cells.

Expression Pattern of Neuroendocrine Cells and Survivin in the Prostate of Rabbits / 대한비뇨기과학회지

PURPOSE: The neuroendocrine cell (NE cell) is thought to play an important role in the development of hormone-refractory prostate cancer. Survivin is one of the IAPs (inhibitors of apoptosis), and it is expressed in the NE cell and in most of the common cancers, but not in normal tissue. The objective of this study was to investigate the expression pattern of the NE cell and survivin in the prostate of rabbits. MATERIALS AND METHODS: The 9 rabbits underwent orchiectomy and their prostates were removed at 0 weeks (control), 2 weeks and 6 weeks after orchiectomy. Each of the prostatic tissue specimens was stained with H&E; immunohistochemical staining was done for chromogranin A, synaptophysin and survivin, and the tissue specimens were then examined by microscopy. RESULTS: In the prostate of rabbits, most of the NE cells were located between the epithelial gland and the stroma. NE differentiation occurred 6 weeks after orchiectomy. The location of cells that were positive for survivin was almost same as that of the NE cells. CONCLUSIONS: The main location of NE cells in the prostate of rabbits was between the epithelial gland and the stroma, and NE differentiation occurred 6 weeks after orchiectomy, the same as in a human or a dog. The location of survivin positive cells coincided with that of the NE cells. Therefore, a rabbit seems to be a suitable animal model for the study of the NE cell.

Tumores neuro-endocrinos del intestino / Neuroendocrine tumors of the small intestine

Los tumores carcinoides son neoplasias poco frecuentes en el tubo digetivo y que se desarrollan a partir de las células que forman el sistema APUD o neuroendocrinas. El objetivo es analizar la nueva nomenclatura, la incidencia en el aparato digetivo, la presentación clínica, diagnóstico y tratamiento quirúrgico

Tumores neuro-endocrinos del intestino / Neuroendocrine tumors of the small intestine

Los tumores carcinoides son neoplasias poco frecuentes en el tubo digetivo y que se desarrollan a partir de las células que forman el sistema APUD o neuroendocrinas. El objetivo es analizar la nueva nomenclatura, la incidencia en el aparato digetivo, la presentación clínica, diagnóstico y tratamiento quirúrgico

Immunohistochemical and electron-microscopical identification of neuroendocrine cells in the respiratory tract of rats with experimental uraemia.

The aim of the present study was to characterise immunohistochemically and ultrastructurally the neuroendocrine cells in the pulmonary systems of uraemic rats. Pieces of lung and trachea were collected 1, 2 and 4 weeks after nephrectomy. Paraffin-embedded sections were stained with H+E and by silver impregnation. For the identification of neuroendocrine cells immunohistochemical reactions were performed with the use of specific antibodies against calcitonin (CT), somatostatin (SOM), synaptophysin (SYN), neuron-specific enolase (NSE) and calcitonin gene-related peptide (CGRP). For electron microscopy, ultrathin sections were used. The analysis showed an increased number of both the solitary neuroendocrine cells and of neuroepithelial bodies in uraemic rats when compared to control animals.

Immunohistochemical and electron-microscopic identification of neuroendocrine cells in the stomach of uremic rats.

Many disturbances in electrolyte and hormonal balance in the body induced by functional impairment of renal parenchyma may affect the activity of amine precursor uptake and decarboxylation (APUD) cells, which constitute a very important link in the regulation of homeostasis. The aim of the present study was the morphological, immunohistochemical and ultrastructural estimation of enteroendocrine cells in the stomach of uremic rats. Fragments of gastric pylorus were collected 1, 2 and 4 weeks after nephrectomy. Paraffin embedded sections were stained with H + E and by silver impregnation. For identification of neuroendocrine cells, immunohistochemical reactions were performed using specific antibodies against somatostatin, synaptophysin, neuron-specific enolase and anti-calcitonin gene related peptide. The analysis showed an increased number of APUD cells in the stomach of uremic rats compared to control rats, which may be a morphological expression of their hyperfunction in the functional impairment of renal parenchyma. These results suggest that chronic renal failure can modulate the secretory processes of APUD cells.

Expression of Neuroendocrine Cells in the Prostate of Rat and Guinea Pig after Orchiectomy / 대한비뇨기과학회지

PURPOSE: Neuroendocrine cells, also referred to as amine precursor uptake and decarboxylation (APUD) cells, in the prostate gland are serotonin and peptide containing cells, which are thought to play an important role in the regulation of growth, cellular differentiation and homeostasis. The expressions of neuroendocrine cells in the prostate differ between species and pathological conditions of the prostate. Androgen is believed to be a major effective material toward the prostate, its role in neuroendocrine cells is uncertain. The objective of this study was to investigate the effects of blockade of androgen on neuroendocrine cells in the prostate of rats and guinea pigs. MATERIALS AND METHODS: Rats and guinea pigs underwent an orchiectomy, and their prostate glands removed at 0 (control), 2 (2-week group) and 6 (6-week group) weeks after the orchiectomy. Each prostate tissue was examined both microscopically and with immunohistochemistry using synaptophysin, chromogranin A and serotonin. RESULTS: In the rat prostate glands, fewer neuroendocrine cells were stained with chromogranin A compared to the other two monoclonal antibodies. Although some atrophy of the glandular structure was presented grossly and microscopically in the castration groups, there was no difference in the chromogranin A immunoreactivity between the control, 2-week and 6-week groups. In the guinea pig prostate glands, few neuroendocrine cells were stained with either synaptophysin or serotonin. Glandular atrophy presented in the castration groups. There was no difference between the control, 2-week and 6-week groups in the immunoreactivities of the synaptophysin and serotonin monoclonal antibodies. CONCLUSIONS: The immunoreactivities of the neuroendocrine cells of rats and guinea pigs were different from those in humans and from each other. Neuroendocrine cells in the prostate of rats and guinea pigs exist only in small numbers, and seem to be independent of androgen.

Expression of Neuroendocrine Cells in the Prostate of Rat and Guinea Pig after Orchiectomy / 대한비뇨기과학회지

PURPOSE: Neuroendocrine cells, also referred to as amine precursor uptake and decarboxylation (APUD) cells, in the prostate gland are serotonin and peptide containing cells, which are thought to play an important role in the regulation of growth, cellular differentiation and homeostasis. The expressions of neuroendocrine cells in the prostate differ between species and pathological conditions of the prostate. Androgen is believed to be a major effective material toward the prostate, its role in neuroendocrine cells is uncertain. The objective of this study was to investigate the effects of blockade of androgen on neuroendocrine cells in the prostate of rats and guinea pigs. MATERIALS AND METHODS: Rats and guinea pigs underwent an orchiectomy, and their prostate glands removed at 0 (control), 2 (2-week group) and 6 (6-week group) weeks after the orchiectomy. Each prostate tissue was examined both microscopically and with immunohistochemistry using synaptophysin, chromogranin A and serotonin. RESULTS: In the rat prostate glands, fewer neuroendocrine cells were stained with chromogranin A compared to the other two monoclonal antibodies. Although some atrophy of the glandular structure was presented grossly and microscopically in the castration groups, there was no difference in the chromogranin A immunoreactivity between the control, 2-week and 6-week groups. In the guinea pig prostate glands, few neuroendocrine cells were stained with either synaptophysin or serotonin. Glandular atrophy presented in the castration groups. There was no difference between the control, 2-week and 6-week groups in the immunoreactivities of the synaptophysin and serotonin monoclonal antibodies. CONCLUSIONS: The immunoreactivities of the neuroendocrine cells of rats and guinea pigs were different from those in humans and from each other. Neuroendocrine cells in the prostate of rats and guinea pigs exist only in small numbers, and seem to be independent of androgen.

Review article--involvement of gastric APUD cells in chronic renal failure.

Uremia leads to a number of metabolic and hormonal disorders induced by renal failure with definite biological and clinical sequels. Most frequently, alimentary disorders are the first to appear, followed by symptoms from other organs and systems. The gastrointestinal tract is a site of synthesis of many compounds that have hormonal or hormonal-like biological activity. These substances are produced by highly-specialised receptor-effector cells, that are dispersed in the gastrointestinal mucosa and classified as APUD cells. The present review is an attempt to make a synthesis of current opinions and views concerning the effect of homeostatic dysfunction of the kidneys on the morphology and action of APUD cells in the stomach.

Chromaffin cells as models of endocrine cells and neurons.

Chromaffin cells have many functional similarities to amine- and peptide-producing endocrine cells throughout the body and to both peripheral and central neurons. The hypothesis of a shared, neural origin for chromaffin cells and most other endocrine cells is not tenable. However, chromaffin cells and their neoplastic counterparts, known as pheochromocytomas, are valuable models for studies of endocrine and neural properties. In this session, PC12 rat pheochromocytoma cells are used in two novel applications: to identify profiles of gene expression that may mediate cell death in neurodegenerative disorders and to study mechanisms for transduction of hypoxic signals. Recently described pheochromocytoma cell lines from neurofibromatosis knockout mice are shown to be novel models for signaling by the receptor tyrosine kinase ret, and purified enterochromaffin-like (ECL) cells are shown to offer new opportunities to study the shared and distinctive aspects of neuroendocrine function using a normal cell type.